The posterior chamber of the eye and, in particular, the retina and associated structures, are critical to vision. Significant vision threatening diseases are associated with these structures, including macular degeneration, diabetic retinopathy, diabetic macular edema, and central and branch vein retinal occlusion. The preferred treatment for many of these conditions is the delivery of an active pharmaceutical ingredient (API) directly to a portion of the eye. However, the anatomy and humor circulation system of the eye present a significant barrier to drug entry, particularly into the posterior chamber and vitreous portions of the eye.
One method of providing treatment to the eye is the injection of an API into the posterior chamber and vitreous portions of the eye. While simple and efficacious, serious side effects may result from repeated syringe needle invasion of the eye globe due to multiple injection treatments. The injection treatment method also limits the total dose that may be applied at a given time and restricts the pharmacokinetic profile that can be achieved. Finally, a disease management program that is based on frequent injections may not be practical or feasible. Multiple injection treatment requires that the patient visit a physician or ophthalmologist for each injection, which may become impractical and expensive for chronic conditions. Furthermore, due to resource constraints, it may be unfeasible for an ophthalmologist to facilitate multiple injection treatment for a large number of patients with chronic conditions.
As an alternative to or in addition to injection treatment, a drug-eluting device may be implanted directly into the eye. These devices are surgically implanted or are injected into the posterior chamber and include gancyclovir and steroid eluting drug components. Commercially available steroid eluting implants include fluocinolone acetonide implants (e.g., Retisert®, Vitrasert®, and Iluvien™) and dexamethasone implants (e.g., Ozurdex®). Typically, such implants release a drug at a constant or slowly changing rate. See, U.S. Pat. Nos. 6,217,895 and 6,548,078 (to Retisert), U.S. Pat. No. 5,378,475 (to Vitrasert), U.S. Pat. Nos. 6,726,918, 6,899,717, 7,033,605, 7,625,582, 7,767,223 (to Ozurdex), and U.S. Patent Pub. 2007/0122483 (to Iluvien), which are incorporated by reference. These implantable devices typically provide a constant pharmacokinetic profile resulting from a continuous drug dosing. This continuous dosing may be acceptable for certain drugs, but for other drugs, continuous dosing can result in serious side effects. For example, continuous delivery of a steroid in the eye results in a high incidence of cataracts or elevated intraocular pressure that may result in glaucoma. Thus, in some cases, it is desirable to reduce the incidence of these side effects by providing a treatment that delivers the drug only when needed.
Another significant challenge in the development of technologies for the delivery of pharmaceutical drugs and, in particular, macromolecule (e.g., peptide and protein) drugs, is the limited stability of these molecules when in contact with water or in an aqueous solution. Many macromolecule drugs, including proteins, that are unstable in aqueous solution are handled and stored as dry solids (“dry” is defined within this document as substantially free of residual moisture, typically with a water content not exceeding 10% water by weight). Delivery systems that store or release macromolecule drugs in liquid or gel form will have limited utility due to accelerated degradation of the drug caused by high residual moisture. If a macromolecule drug can be kept in a dry, solid form, its degradation can be minimized and a long-term implantable device is possible. See, Elizabeth R. Proos, James H. Prescott and Mark A. Staples “Long-term Stability and In Vitro Release of hPTH(1-34) from a Multi-reservoir Array” Pharmaceutical Research, Volume 25, Number 6, 1387-1395 (Feb. 12, 2008). It is therefore desirable to create a drug delivery system that stores a drug in a dry, solid form and that prohibits or limits any moisture from passing through the device and into the drug, until such time that release of the drug is desired.
Moisture transport into or out of a drug delivery device can be prohibited or limited through the use of a low-permeability barrier constructed using hermetic materials and the use of hermetic sealing techniques. Stability of a macromolecule drug may be increased if it is formulated with excipients that enhance or maintain the molecule's stability, if it is stored with its optimal residual moisture content, and if the residual moisture content is maintained with a hermetically-sealed barrier reducing the transport of water into or out of the drug formulation.
It is known that metallic films on silicon wafer wells to perform long-term sealing of APIs in an electro-thermally-activated drug delivery device (DDD). This approach allows for hermetic or highly impermeable DDDs. For example, see U.S. Pat. Nos. 6,976,982, 7,776,024, 7,582,080, 7,226,442, 6,808,522, 5,797,898, 7,488,316, 6,827,250, 7,114,312, and 7,497,846 and U.S. Pub. Nos. 2006/0115323 A1, 2008/0221557, 2008/0221555, 2008/0172043, 2008/0083041, 2008/0015494, 2008/0071252 A1, 2007/0275035 A1, 2009/0142386 A1, 2004/0247671 A1, and 2010/0119604 A1, assigned to MicroCHIPS, which are hereby incorporated by reference.
Thus, there is need for an implantable drug delivery device that provides a low-permeability barrier to protect a sensitive drug payload, and is also capable of laser activation so that a drug dosing can be initiated using noninvasive techniques.